Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

Schizophrenia and bipolar disorder are two distinct
diagnoses that share symptomology. Understanding
the genetic factors contributing to the shared and
disorder-specific symptoms will be crucial for
improving diagnosis and treatment. In genetic data
consisting of 53,555 cases (20,129 bipolar disorder
[BD], 33,426 schizophrenia [SCZ]) and 54,065 controls,
we identified 114 genome-wide significant loci
implicating synaptic and neuronal pathways shared
between disorders. Comparing SCZ to BD (23,585
SCZ, 15,270 BD) identified four genomic regions
including one with disorder-independent causal
variants and potassium ion response genes as
contributing to differences in biology between the
disorders. Polygenic risk score (PRS) analyses identified
several significant correlations within case-only
phenotypes including SCZ PRS with psychotic features
and age of onset in BD. For the first time, we
discover specific loci that distinguish between BD
and SCZ and identify polygenic components underlying
multiple symptom dimensions. These results
point to the utility of genetics to inform symptomology
and potential treatment.